Although the pathogenesis of multiple sclerosis (MS) remains unknown, current immunologic studies imply both humoral and cellular immune dysfunction in MS. These findings have raised the possibility of an autoimmune basis which provides the rationale for a variety of immunosuppressive therapies that have been proposed and tested in progressive MS. In this study we will treat MS patients with 2- chlorodeoxyadenosine (2-CdA), a new selective immunosuppressive nucleoside developed at Scripps Clinic for the treatment of certain leukemias, lymphomas and autoimmune disorders and already administered to over 600 patients with such disorders. We have concluded a pilot study to determine if 2-CdA is well-tolerated and effective in patients with progressive MS. In this study there was evidence of partial improvement of neurologic function in each of the four patients studied. Of particular importance was the fact that 2-CdA showed no evidence of clinically significant toxicity in MS patients with normal bone marrow function, and side effects of the medication have been imperceptible in the patients so far studied. We now plan a Phase II randomized, double-blinded, placebo-controlled trial of 2-CdA in patients with progressive MS. The first portion of this study will be a parallel design in which randomized, matched pairs of patients receive either 2-CdA or placebo through a surgically implanted, semi- permanent central line. If interim analysis after six months of treatment does not show a statistically significant effect, patients who received 2- CdA will be crossed-over after a six month wash-out to placebo, and similarly, patients who received placebo will be crossed-over to active drug. This will provide us with an opportunity to determine whether this drug has a statistically significant effect on the clinical course and laboratory manifestations of multiple sclerosis. Our studies will also provide us with the opportunity to make observations regarding the effect of 2-CdA on lymphocyte and monocyte subsets in patients without bone marrow disease.